CANCER GENETICS AND GENOMICS PROGRAM Joseph Nevins, Ph.D. and Huntington Willard, Ph.D., Co-Leaders The Cancer Genetics and Genomics Program includes a group of 26 outstanding investigators making important and major contributions to the understanding of the molecular mechanisms underlying oncogenesis as well as the identification of genes that contribute to and confer susceptibility to cancer. This is a very interactive and integrated group of investigators that forms a cohesive unit focused on the common goals ot identifying genes involved in oncogenesis and their role in the development of human cancer. The activities of the program are organized into three specific areas of scientific focus that include cancer genetics, with a focus on the identification of genes that define risk of onset for disease;cancer genomics, that involves programs applying technologies, particularly DNA microarray analysis, to better understand the characteristics of tumors;and oncogenic mechanisms and pathways, focused on the gene activities known to participate in the oncogenic process. These three aspects of the Program are tightly integrated and exceedingly synergistic with work flowing between each to influence the activities of the others. Indeed, we view a major strength of the Cancer Genetics and Genomics program to be the interrelated activitydiscoveries in work on oncogenic signaling pathways feeds the cancer genetics and genomics activities. Conversely, advances made in genomic applications to cancer outcome has impacted on the study of oncogenic pathways. Moreover, the identification of genes that are prognostic for cancer outcomes, based on gene expression profiling work, leads directly to candidates for study in case-control association analyses of cancer risk. Perhaps the most important development within the Program that has added value to the overall cancer research effort at Duke is the formation of a multidisciplinary research program concerned with the creation, modeling, analysis and integration of multiple forms of data in basic and clinical biomedical studies. The applied contexts focus heavily in projects involving molecular characterization of breast cancer and other cancers including ovarian and brain. This program is central to the activities of the Cancer Genetics and Genomics Program and includes the majority of the Program members.